Mifepristone's mechanism of action in medical abortion differs from its anti-glucocorticoid action. In abortion at 7 weeks gestation, mifepristone acts by:

• A Competitive antagonism at progesterone receptors (PR-A and PR-B), causing cervical ripening (Cx softening via PGE2 upregulation), uterine sensitization to prostaglandins, and decidual breakdown ✓
• B Direct COX-2 induction in decidual cells, generating prostaglandins independently of progesterone receptor blockade
• C GnRH receptor downregulation in the pituitary, reducing LH and hCG support of the corpus luteum, withdrawing progesterone production
• D Inhibition of 3β-HSD in the corpus luteum, preventing progesterone synthesis and withdrawing trophoblast support

Explanation

Mifepristone (RU-486) is a 19-norsteroid that antagonizes both progesterone receptors (PR-A and PR-B) and glucocorticoid receptors. In early pregnancy, PR antagonism: (1) causes decidual breakdown (endometrial degeneration) and reduces hCG production, ultimately withdrawing corpus luteum support; (2) increases prostaglandin sensitivity of myometrium and cervix by upregulating prostaglandin receptors and COX-2 enzyme expression; (3) directly softens the cervix. Misoprostol (prostaglandin E1 analogue) is added 24–48 hours later for uterine contractions. The anti-glucocorticoid effect can paradoxically increase cortisol levels (pituitary feedback compensation) at high doses.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.